Da'dara Akram A, Siddons Giles, Icaza Melissa, Wang Qiang, Skelly Patrick J
Molecular Helminthology Laboratory, Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536, USA.
Mol Biochem Parasitol. 2017 Jul;215:40-46. doi: 10.1016/j.molbiopara.2016.12.007. Epub 2016 Dec 21.
Schistosomes are intravascular parasitic worms that cause the debilitating disease schistosomiasis. To better understand how these long-lived parasites may subvert host immune and hemostatic capabilities, we examine here the impact of adult Schistosoma mansoni worms on the human serum proteome. Normal human serum (150μl) was incubated at 37°C for one hour either in the presence or absence of adult worms (∼50 pairs). Thereafter parasites were removed, serum samples were labeled and their proteins resolved for comparative analysis by 2D-Differential in-Gel Electrophoresis (2D-DIGE). Several differences were noted between the two samples. Twenty protein spots were recovered and identified following trypsin digestion and mass spectroscopy. Strikingly, most of these (11/20) are associated with the complement system and include complement components C3, C4, factor B, complement factor H related protein 1 and clusterin. Western blot analysis confirms the impact of the worms on C3, C4 and factor B in serum. The data suggest that schistosomes engage complement but can rapidly degrade selected complement proteins which may help explain the worm's refractoriness towards complement-mediated attack. Other serum proteins identified as being impinged upon by schistosomes are alpha 2 macroglobulin, alpha 1 anti-chymotrypsin, actin cytoplasmic 2, serum amyloid A-4, protein DDX26B, hemoglobin subunit B and serum albumin. While the molecular nature of the interaction between these proteins and schistosomes is not known, possible roles for some of them in hemostasis, immune evasion and in the host response to serum stress are suggested.
血吸虫是血管内寄生蠕虫，可导致使人衰弱的血吸虫病。为了更好地了解这些长寿寄生虫如何颠覆宿主的免疫和止血能力，我们在此研究了曼氏血吸虫成虫对人血清蛋白质组的影响。将正常人血清（150μl）在37°C下孵育一小时，分别在有或没有成虫（约50对）的情况下进行。之后去除寄生虫，对血清样本进行标记，并通过二维差异凝胶电泳（2D-DIGE）分离其蛋白质以进行比较分析。在两个样本之间发现了一些差异。经胰蛋白酶消化和质谱分析后，回收并鉴定了20个蛋白点。令人惊讶的是，其中大多数（11/20）与补体系统相关，包括补体成分C3、C4、B因子、补体因子H相关蛋白1和簇集蛋白。蛋白质印迹分析证实了蠕虫对血清中C3、C4和B因子的影响。数据表明，血吸虫会激活补体，但能迅速降解某些选定的补体蛋白，这可能有助于解释蠕虫对补体介导攻击的抗性。其他被确定受血吸虫影响的血清蛋白包括α2巨球蛋白、α1抗糜蛋白酶、肌动蛋白细胞质2、血清淀粉样蛋白A-4、蛋白质DDX26B、血红蛋白亚基B和血清白蛋白。虽然这些蛋白质与血吸虫之间相互作用的分子性质尚不清楚，但提示其中一些蛋白在止血、免疫逃避以及宿主对血清应激的反应中可能发挥的作用。
